Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice
Martínez Muriana, Anna (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Pastor, Diego (UMH-CSIC. Instituto de Neurociencias)
Mancuso, Renzo (KU Leuven. VIB Center for Brain and Disease Research)
Rando, Amaya (Universidad de Zaragoza. Laboratorio de Genética Bioquímica)
Osta, Rosario (Universidad de Zaragoza. Laboratorio de Genética Bioquímica)
Martínez, Salvador (UMH-CSIC. Instituto de Neurociencias)
López Vales, Rubèn (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Navarro, X. (Xavier) (Xavier) (Universitat Autònoma de Barcelona. Facultat de Medicina)

Fecha:	2020
Resumen:	The simultaneous contribution of several etiopathogenic disturbances makes amyotrophic lateral sclerosis (ALS) a fatal and challenging disease. Here, we studied two different cell therapy protocols to protect both central and peripheral nervous system in a murine model of ALS. Since ALS begins with a distal axonopathy, in a first assay, we performed injection of bone marrow cells into two hindlimb muscles of transgenic SOD1 G93A mice. In a second study, we combined intramuscular and intraspinal injection of bone marrow cells. Fluorescence-activated cell sorting was used to assess the survival of the transplanted cells into the injected tissues. The mice were assessed from 8 to 16 weeks of age by means of locomotion and electrophysiological tests. After follow-up, the spinal cord was processed for analysis of motoneuron survival and glial cell reactivity. We found that, after intramuscular injection, bone marrow cells were able to engraft within the muscle. However, bone marrow cell intramuscular injection failed to promote a general therapeutic effect. In the second approach, we found that bone marrow cells had limited survival in the spinal cord, but this strategy significantly improved motor outcomes. Moreover, we also found that the dual cell therapy tended to preserve spinal motoneurons at late stages of the disease and to reduce microgliosis, although this did not prolong mice survival. Overall, our findings suggest that targeting more than one affected area of the motor system at once with bone marrow cell therapy results in a valuable therapeutic intervention for ALS.
Ayudas:	Agencia Estatal de Investigación SEV-2013-0317
Nota:	Altres ajuts: Instituto de Salud Carlos III of Spain, co-funded by European Union. Project number: ERDF/ESF, "Investing in your future"
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	ALS ; SOD1 ; Bone marrow ; Stem cells ; Motoneuron disease
Publicado en:	Stem cell research & therapy, Vol. 11 (february 2020) , ISSN 1757-6512

DOI: 10.1186/s13287-020-1573-6
PMID: 32033585

11 p, 4.3 MB

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